Project Summary/Abstract for CT Imaging Core The development of high-resolution micro-CT (CT) during the past two decades has revolutionized the quantitative assessment of calcified and X-ray dense tissue morphology. With the capability of non-destructive, three-dimensional (3D) visualization of tissue structure, CT has largely supplanted traditional histomorphometry and become a gold standard for calcified tissue density and microstructure evaluation for many measures. Due to the low intrinsic X-ray contrast of non-mineralized tissues, traditional applications of CT in musculoskeletal research have been limited to mineralized tissue. However, the development of contrast-enhanced imaging methods has greatly broadened applications of CT to include musculoskeletal soft tissues as well. These cutting-edge image-based quantification methods not only enable characterization of soft-tissue morphology, but some also yield insight into tissue composition, such as glycosaminoglycan (GAG) density, which is associated with soft-tissue function and mechanics. Another important advance in the past decade is in vivo CT imaging of living small animals. Research of musculoskeletal tissue injury and repair has been progressively utilizing animal models of human disease. Unlike many assays that require sacrificing the animal to extract tissues for analysis, in vivo CT enables longitudinal evaluation of changes in a particular animal non-invasively over time. This new imaging strategy minimizes the number of animals required while enhancing statistical power. With these developments, CT can now provide a deep and quantitative understanding of the genetic influences on the skeleton, as well as remodeling events in hard and soft tissues during repair, treatment, and with altered loading scenarios. Further, a CT modality for clinical imaging of calcified tissue microstructure, called high-resolution peripheral quantitative CT (HR-pQCT), has recently been developed. This technology inaugurated a new era of non-invasive quantitative skeletal imaging, and has become a powerful tool for clinical research of musculoskeletal disorders. The overall objective of the CTIC is to offer a wide range of CT imaging approaches to evaluate musculoskeletal tissue injury and repair, and to provide training and consultation for new projects and collaborations utilizing these assays. The Specific Aims for the CTIC are: 1) To provide guidance and expertise on the use of CT imaging for musculoskeletal research through educational enrichment programs and one-on-one interactions, 2) To provide a range of CT imaging resources, expertise, and services for the study of the structure, function and physiology of the musculoskeletal system in laboratory animals and humans, 3) To develop new CT imaging-based techniques that will be applicable to musculoskeletal research, and 4) To provide funding for the development of new projects and collaborations and to develop preliminary and/or feasibility data for investigators.